Children’s Hospital on cusp of gene therapy breakthrough

Children’s Hospital on cusp of gene therapy breakthrough

Local researchers are awaiting the green light to test a cutting-edge cure for a devastating disease that leaves babies unable to fight off the simplest infections.

Cincinnati Children’s Hospital Medical Center has gotten permission from the U.S. Food and Drug Administration to test a gene therapy treatment against X-linked severe combined immunodeficiency, or so-called “bubble-boy” disease. It’s the first federal approval the Corryville hospital has received for a gene therapy treatment conceived and manufactured in its own lab.

Now, Alexandra Filipovich and her colleagues are waiting for the hospital’s own institutional review board to sign off the trial.

“We’re ready to go,” said Filipovich, director of the hospital’s immunodeficiency and histiocytosis program and the primary investigator for the trial.

Maverick Steiner was only 4 months old when he was diagnosed with the disease after a long run of illnesses, including ear infections and diarrhea that wouldn’t go away. Doctors grew worried when he developed a form of pneumonia normally seen in AIDS patients – a sign his immune system was seriously compromised.

The immune disorder is caused by a defective gene that leaves babies unable to make two types of cells that attack bacteria, viruses and certain cancers.

For most babies, including Maverick, a bone marrow transplant cures the disease. But 20 to 30 percent of babies born with the disorder can’t get a transplant. Either they can’t find a donor match or they’re too sick to withstand the procedure.

For those babies, gene therapy could be the answer. It relies on technology that lets doctors custom-tailor viruses that, instead of causing sickness, cure it.

For Filipovich’s experiment, researchers will collect stem cells from babies with the immune disorder.

In the lab, those stem cells will be infected with specially designed viruses that carry a functioning copy of the defective gene that causes the immune disorder. The viruses have been engineered so that they can’t cause illness.

Doctors then will put the stem cells with the functioning gene back in the babies through an IV. If the experiment works, the new gene will let the babies’ immune systems function normally, and they’ll be able to fight off infections.

The viruses carrying the new gene were designed and built at Cincinnati Children’s.

The idea of using viruses to attack disease has great potential for treating cystic fibrosis, Huntington’s disease, sickle cell anemia and some forms of cancer, including brain tumors, said Han van der Loo, the lab’s director. It also has the potential to attract world-class researchers, coveted federal research dollars and private pharmaceutical contracts.

Dr. Punam Malik, a hematology-oncology expert and co-director of the lab, came to Cincinnati because of the viral vector lab.

Malik, now the lab’s co-director, is heading up a clinical trial testing gene therapy as a potential cure for sickle-cell anemia. The trial could start in the spring of 2011.

Malik is organizing a clinical trial to test gene therapy as a potential cure for sickle cell anemia. She’s still waiting for approval from federal regulators.

It’s taken Malik and her colleagues 10 years to get to this point – and the therapy hasn’t been injected into a human being yet. It has been tested in lab animals, but the altered viruses had to be designed and manufactured, and that process costs money.

Without the in-house lab, Malik said, she and her colleagues would have had to contract with another research-grade lab, which would have required them to put the science on hold while they found money. “We can’t afford to do that,” she said.

To produce the altered viruses in both the quantity and quality suitable for use in humans, Malik and other researchers without access to an in-house lab would likely need to turn to the pharmaceutical industry. But the industry isn’t likely to be interested in producing an extremely expensive drug that might not work.

“They don’t want to take a risk. They want a return on investment, and we have no idea if we will have a return on investment,” she said.

Because Cincinnati Children’s has its own viral vector lab and its own lab for processing pharmaceutical-quality stem cells, the pressure to make a profit is off. Researchers like Malik just have to find enough money to cover the cost of labor and materials.

The viral vector lab, a 10,000-square foot facility with nine “clean rooms” in which technologists make the altered viruses, has the capacity to make a gene therapy drug in sufficient quantities for small-scale human testing. Filipovich hopes to recruit three patients through the hospital for the first phase of her immune disorder experiment.

If a gene therapy drug were found to be safe and effective enough to go onto large-scale trials – meaning it was likely to win FDA approval and make it to the market – the hospital would likely license, or sell, the drug to a pharmaceutical company.

Such a sale, which could mean millions of dollars.

The hospital is already expecting other kinds.

Because of the XSCID trial, Filipovich and her colleagues are getting invitations from researchers in Europe to participate in a number of projects. There’s no way to put a price tag on that kind of opportunity, she said.

For parents, there’s no way to put a price tag on their children’s health.

Maverick, now 16 months old, is doing well since the bone marrow transplant, said his mother, Jessica Steiner. She and her husband, Ryan, live in St. Bernard.

But Maverick spent nearly four months in the hospital while he was waiting for the bone marrow transplant, which he underwent in October.

“He’s doing great now,” she said.

CORRECTION: An earlier version of this story incorrectly spelled the name of Dr. Punam Malik

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